Dissertation / PhD Thesis/Book

PreJuSER-37412

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Markierungsverfahren zur Synthese 4-[$^{18}$F]Fluorprolyl-haltiger Peptide

Jelinski, M. (Corresponding Author)FZJ*

2003
Forschungszentrum, Zentralbibliothek Jülich

Please use a persistent id in citations: http://hdl.handle.net/2128/234

Report No.: Juel-4008

Abstract: The requirement of selective radiopharmaceuticals for PET-diagnostics necessitates the development of new labelling methods taking into account the substantial and structural diversity of the compounds to be labelled . Therefore different concepts for $^{18}$F-fluorination of peptides, which are increasingly important as pharmaceuticals, via proline moieties were explored and evaluated in this work. The direct nucleophilic kryptate based $^{18}$F-fluorination of the model peptide Z-Pro-Leu-Gly-4- (4R)-(TsO)Pro-OMe showed, that the peptide is not stable under the basic labelling conditions, and as a result the $^{18}$F-fluorination is not possible. Perfluorbutane-l-sulfonyl[ $^{18}$F]fluoride is a possible reagent for $^{18}$F-fluorination of sensitive hydroxy groups containing biomolecules due to the mild reaction conditions at which aliphatic alcohols are fluorinated by this reagent. By kryptate catalysed, nucleophilic $^{18}$F-fluorination of N,N-bis(perfluorobutane-l-sulfonyl)aniline and evaporation of the active product no-carrier-added perfluorobutane-l-sulfonyl[ $^{18}$F]fluoride can be achieved either dissolved in toluene (RCY: 83 ± 3 %) or adsorbed an a polystyrole-matrix (LiChrolut$^{®}$ EN) with a total yield of 75 ± 6 %. In the presence of an equimolar amount of perfluorobutane-1-sulfonylfluoride as carrier N-Boc-Hyp- OMe can be $^{18}$F-fluorinated with a radiochemical yield of > 90 % and the two model peptides Z-Pro- Leu-Gly-Hyp-OMe and Z-Gly-Leu-Hyp-Gly-Leu-OMe with 40 - 45 % and 30 - 35 %, while in the case of no-carrier-added synthesis only ca. 1 % of the $^{18}$F-fluoroproduct is obtained . The necessary addition of perfluorobutane-l-sulfonylfluoride carrier allows naturally only the synthesis of radiotracers with low molar activity. For performance of the $^{18}$F-fluorination via perfluorobutane-l-sulfonyl[ $^{18}$F]fluoride of the model peptide N-Boc-Hyp-Leu-OH, which is covalently bound to a Wang resin via the C-terminus, the $^{18}$F-fluorination reagent is prepared in absence of a solvent and adsorbed an the Wang resin with a yield of 31 ± 3 %, based on [$^{18}$F]fluoride. The subsequent $^{18}$F-fluorination of the peptide, which was done in the presence of an equimolar amount of perfluorobutane-1-sulfonylfluoride, proceeds with a radiochemical yield of merely 4 ± 1 %. Altematively, the condensation of 4-[$^{18}$F]fluoroproline-methylester via TBTU at the C-terminus of Z-Pro-Leu-Gly-OH could be carried out under no-carrrier-added conditions with a radiochemical yield of 70 - 80 %. The required 4-[$^{18}$F]fluoroproline-methylester could be achieved with a radiochemical yield of 30 - 40 % by $^{18}$F-substitution of N-Boc-trans-4-(ptoluenesulfonyloxy)- proline-methylester, by which the trans-product is also formed in addition to the cis-product, and the cleavage of the Boc group. As a result of these studies another prosthetic group is available for no-carrier-added labelling of peptides.

Note: Record converted from VDB: 12.11.2012
Note: Köln, Univ., Diss., 2002

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Contributing Institute(s):

1. Institut für Nuklearchemie (INC)

Research Program(s):

1. Neurowissenschaften (L01)

Appears in the scientific report 2003
Notes: Nachtrag

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Database coverage:

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